Cell Transplant Repairs Diseased Nervous System In Dogs

December 31, 1996

Application Seen For Multiple Sclerosis In Humans

MADISON -- In a hopeful new development for people with multiple sclerosis (MS), researchers have shown in studies with dogs that they can repair diseased areas of the spinal cord by transplanting nervous system cells into the animals.

Scientists at the University of Wisconsin School of Veterinary Medicine and collaborators report the finding in the current issue of the journal Nature Medicine.

"We are cautiously optimistic that the success we have achieved in dogs may become the best hope available for repair of lesions in people with chronic MS and related disorders," said Dr. Ian Duncan, professor of Veterinary Medicine, who directed the research. "But several scientific questions must be answered before testing in humans can begin. We hope to have these answers within the next two years."

Duncan stressed that transplant therapy for MS would need to be combined with drugs that lessen or prevent on-going disease. While MS is usually widespread throughout the central nervous system, in many patients it causes chronic lesions of the spinal cord, and such patients might be appropriate first candidates for the therapy, he said.

MS is a complex, chronic disease affecting myelin, the sheaths that surround nerve cells. Patches of demyelination, or lesions, along nerve cells can result in weakness, incoordination, and speech and vision disturbances. As many as 300,000 people in the United States have MS, which usually strikes young adults.

Some MS researchers have been encouraged by the recent success of fetal tissue transplantation into patients with Parkinson1s disease, noted Duncan.

"This has been an important precedent," he said. "These advances have shown us that nerve cells can be transplanted safely and effectively, and can survive long-term in the human brain without significant complications in the majority of patients."

Buoyed by the Parkinson1s transplant experiences and progress resulting from his own years of research and that of others on myelinating disorders in rodents, Duncan recently turned his attention to a family of dogs born with a genetic mutation affecting central nervous system myelin. Although not identical to MS, the dog model offers many similarities.

Researchers transplanted glial cells, the supporting structure of nervous system tissue, from healthy newborn pups or fetuses into six of the abnormal dogs ranging in age from two to 32 weeks. All of the dogs exhibited myelin growth at the site of the transplant and in adjacent areas, including one dog in which growth was noted for 27 weeks.

"A dramatic result of these experiments was the degree of myelination - seen as thick and well-compacted sheathing - achieved by the transplanted cells," said Duncan. "However, the extent of myelination in dogs that received the fetal glial cells was even more remarkable."

The fetal cell transplants yielded growth well beyond the graft site, said Duncan, noting that migration of the cells and subsequent myelination was far greater than he and others had observed in earlier experiments with rodents. The experiments in dogs were the most relevant to humans undertaken to date, he added.

The UW scientist was especially encouraged to observe that nerve cells in the mature dog could also be myelinated by the transplanted glial cells. "This is encouraging with regard to human transplantation, since most myelin disorders in humans occur in early adulthood," he said.

MS and spinal cord injuries can also produce gliosis, a reaction that results in excess tissue around demyelinated nerve cells that may serve as a barrier to remyelination. Gliosis also occurs naturally with age in the dogs Duncan studied.

"We showed we could transplant cells into a mature animal with gliosis and still achieve significant myelination," he said. "This has started us thinking that gliosis in MS may not be an absolute barrier to repair, as previously believed."

Duncan said his group has targeted MS with this research, but several other disorders characterized by demyelination may benefit from the transplant technique.

The Wisconsin work is supported by the National Institutes of Health, National Multiple Sclerosis Society and the Myelin Project, an international task force of scientists working on myelin and remyelination founded by Augusto and Michaela Odone of Lorenzo's Oil fame.

University of Wisconsin-Madison

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